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Jonathan A. Epstein, M.D.

William Wikoff Smith Professor of Cardiovascular Research
Department: Medicine
Graduate Group Affiliations

Contact information
Executive Vice Dean and Chief Scientific Officer
602 PCAM South Expansion
3400 Civic Center Blvd.
Philadelphia, PA 19104
Office: (215) 898-8731
Fax: (215) 573-2030
A.B. (Biochemistry)
Harvard College, 1983.
M.D. (Medicine)
Harvard Medical School, 1988.
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Description of CVI Expertise

Executive Vice Dean and Chief Scientific Officer

Research Interests Epigenetic regulation of stem cell biology, developmental biology, and cardiovascular medicine.
Key words: Cardiac development, Neural crest, Transcription, Epigenetics, Stem cells, Nuclear architecture, Hopx.
Research Description The Epstein laboratory is interested in molecular mechanisms of cardiovascular development and stem cell biology, and the implications of these mechanisms for understanding human disease. Transgenic and knockout mouse models are used. The lab has a longstanding history in the genetic causes of congenital heart disease and transcriptional regulation of cell fate determination. Most recently, the lab has focused on epigenetics, including the role of histone deacetylases in cardiac development and adult heart function. Active projects involve the understanding of the packaging of DNA and chromatin in the nucleus in three dimensions (“nuclear architecture”) and the regulation of cell differentiation by protein complexes that tether regions of the genome to the nuclear periphery. The lab has pioneered the concept that entire gene programs that define cardiac cell types can be regulated through interactions between the nuclear lamina and the chromatin. The Epstein lab discovered the tumor suppressor and stem cell gene Hopx and continues to study its role in the heart and in numerous tissue-specific adult resident stem cells including those in the central nervous system, the intestine and the skin. Finally, the lab is using novel methods of engineering immune cells to develop proof-of-principle approaches for treating common cardiovascular disorders.

Selected Publications

Pauerstein PT, Tellez K, Willmarth KB, Park KM, Hsueh B, Arda HE, Gu X, Aghajanian H, Deisseroth K, Epstein JA, Kim SK.: A radial axis defined by Semaphorin to Neuropilin signaling controls pancreatic islet morphogenesis. Development 144(20): 3744-3754, Oct 2017.

Pleshko, A., Shah, P.P., Gupta, M., Babu, A., Moreley, M., Manderfield, L.J., Ifkovits, J.L., Dubois, N., Morrisey, E.E., Lazar, M.A., Smith, C.L., Epstein, J.A., Jain, R.: Geome–nuclear lamina interactions regulate progenitor cell lineage restriction during cardiogenesis. Cell 171(3): 573-587, Oct 2017.

Palpant, N.J., Wang, Y., Hadland, B., Zaunbrecher, R.J., Redd, M., Jones, D., Pabon, L., Jain, R., Epstein, J.A., Ruzzo, W.L., Zheng, Y., Bernstein, I., Margolin, A., Murry, C.E.: Chromatin and Transcriptional Analysisof Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis. Cell Reports 20: 597-608, Aug 2017.

Ramjee, V., Li, D., Manderfield, L.J., Liu, F., Engleka, K.A., Aghajanian, H., Rodell, C.B., Lu, W., Ho, V., Wang, T., Li, L., Singh, A., Cibi, D.M., Burdick, J.A., Singh, M.K., Jain, R., Epstein, J.A.: Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction. J Clin Invest 127(3): 899-911, Mar 2017.

Loh, K.M., Chen, A., Koh, P.W., Deng, T.Z., Sinha, R., Tsai, J.M., Barkal, A.A., Shen, K.Y., Jain, R., Morganti, R.M., Shyh-Chang, N., Fernhoff, N.B., George, B.M., Wernig, G., Salomon, R.E., Chen, Z., Vogel, H., Epstein, J.A., Kundaje, A., Talbot, W.S., Beachy, P.A., Ang, L.T., Weissman, I.L.: Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types. Cell 166(2): 451-67, July 2016.

Aghajanian, H., Cho, Y.K., Manderfieldm L.J., Herling, M.R., Gupta, M., Ho, V.C., Li, L., Degenhardt, K., Aharonov, A., Tzahor, E., Epstein, J.A.: Coronary vasculature patterning requires a novel endothelial ErbB2 holoreceptor. Nat Commun 7: 12038, June 2016.

Singh, A., Ramesh, S., Cibi1, D.M., Yun, L.S., Li, J. Li, L., J. Manderfield, L., Olson, E.N., Epstein, J.A. and Singh, M.K.: Hippo signaling mediators Yap and Taz are required in the epicardium for coronary vasculature development. Cell Reports 17(15): 1384-93, May 2016.

He, S., Mansour, M.R., Zimmerman, M.W., Ki, D.H., Layden, H.M., Akahane, K., Gjini, E., DeGroh, E.D., Perez-Atayde, A.R., Zhu, S., Epstein, J.A., Look, A.T.: Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain eLife 5:e14713, 2016.

Li, D., Takeda, N., Jain, R., Manderfield, L.J., Liu, F., Li, L., Anderson, S.A., Epstein, J.A.: Hopx distinguishes hippocampal from lateral ventricle neural stem cells. Stem Cell Res 15(3): 522-529, Oct 2015.

Yzaguirre, A.D., Padmanabhan,A., de Groh, E.D., Engleka, K.A., Li, J., Speck, N.A., Epstein, J.A.: Loss of neurofibromin Ras-GAP activity enhances the formation of cardiac blood islands in murine embryos. eLife 4, Oct 2015.

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Last updated: 05/23/2018
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